Overview: Karen Mustian, Ph.D., an exercise psychologist, is applying for a mentored career development award to expand her research skills and become an independent investigator in cancer control. Her goal is to contribute to the understanding of exercise interventions for reducing the side effects of cancer treatments, specifically, cancer-related fatigue (CRF);the most prevalent side effect in patients. The proposed project is theoretically guided by CRF research and de/conditioning theory positing reduced physical activity results in loss of muscle mass and strength, and resistance exercise improves both. Career Development Plan: Dr. Mustian's previous research and training in exercise psychology, behavioral medicine, and cancer control provide a strong foundation that will be enhanced by the educational plan of specific measurable learning in research skills, cancer control, integrative systems biology and physiology, and health technology. Her primary mentor, Gary Morrow, Ph.D., has been a leader in cancer control research, and training for 30 years. He will contribute expertise in cancer and side effect management and in randomized clinical trial design and analyses. Dr. Mustian's co-mentors also have exceptional experience training researchers. Alice Pentland, M.D. will contribute expertise in cancer biology, and interdisciplinary research to create health technology for quantitative assessment. Anne McTiernan, M.D., Ph.D. will contribute expertise in exercise and cancer. Advisory board members will also contribute their unique expertise to Dr. Mustian's career development. Research Plan: The proposed research project is a randomized clinical trial to expand the positive findings of a feasibility study and examine the influence of a home-based walking and progressive resistance exercise program on CRF in 114 breast cancer patients undergoing radiation. Secondary research goals are to provide pilot information on potential CRF etiological factors, including skeletal muscle mass loss, strength changes, and dysregulation of inflammatory responses associated with the proteasome ubiquitin pathway, and on the use of actigraphy motion data as an independent marker of CRF. These results will help elucidate the public health impact of exercise on CRF, assist in tailoring exercise interventions for CRF, provide pilot data on potential etiological factors and independent markers of CRF for a future R01 study, and position Dr. Mustian to successfully transition to an independent investigator and leader in cancer control science.